The induction of plasmacytomas (PCTs) in the peritoneal cavity of BALB/cAn mice by plastics, paraffin oils or silicone gels is a model system for identifying the steps and stages of neoplastic development. An early oncogenic event in plasmacytomagenesis (PCTgenesis) is a chromosomal translocation that illegitimately recombines c-myc with an Ig locus gene resulting in deregulation of c-myc transcription. The focus of the work in the last year has been on determining when and where the chromosomal translocations take place. Recent evidence from a highly sensitive nested PCR detection method indicates this step probably takes place before the introduction of the peritoneal inducing agent, i.e., in active B lymphocyte populations, e.g., Peyer's patches. Many of the steps in PCTgenesis take place in the chronic inflammatory microenvironment of the oil granuloma. Silicone gels are highly efficient inducers of the microenvironment that permits progression. In contrast, silicone fluids containing long chains are virtually ineffective. We are attempting to identify the active components and properties of silicone gels that are responsible for PCT progression and have evidence that it is the chronic release of low molecular weight dimethylpolysiloxanes from the gel that is the plasmacytomagenic principal. A relatively high incidence of polyreactive myeloma proteins have been in silicone gel evoked PCTs. A second consistent tumor suppressor phenotype, i.e., loss of functional TGF-beta receptors has been identified. Pursuing the basis for the dramatic inhibition of PCTgenesis by the NSAID, indomethacin, we have found that PCT cells possess functional PGE2 receptors, but only develop modest elevations in intracellular cAMP, further PGE2 alone does not initiate cell death in PCTs, but PGE2 plus IBMX, or forskolin alone, both of which raise cAMP 2-3 fold higher do trigger cell death. We are using plasma cells that accumulate in lymph nodes of IL-6 transgenic mice as normal plasma cells which have functional TGF-beta receptors and develop elevated cAMP responses to PGE2.